Starting from simple clinical statistics, the spectrum of methods used in epilepsy research in the Institute of Physiology of the Czechoslovak (now Czech) Academy of Sciences progressively increased. Professor Servít used electrophysiological methods for study of brain activity in lower vertebrates, neuropathology was focused on electronmicroscopic study of cortical epileptic focus and ion-sensitive microelectrodes were used for studies of cortical direct current potentials. Developmental studies used electrophysiological methods (activity and projection of cortical epileptic foci, EEG under the influence of convulsant drugs, hippocampal, thalamic and cortical electrical stimulation for induction of epileptic afterdischarges and postictal period). Extensive pharmacological studies used seizures elicited by convulsant drugs (at first pentylenetetrazol but also other GABA antagonists as well as agonists of glutamate receptors). Motor performance and behavior were also studied during brain maturation. The last but not least molecular biology was included into the spectrum of methods. Many original data were published making a background of position of our laboratory in the first line of laboratories interested in brain development.

• MeSH
• Academies and Institutes MeSH
• Biomedical Research trends   MeSH
• History, 20th Century MeSH
• History, 21st Century MeSH
• Epilepsy * physiopathology   MeSH
• Humans MeSH
• Brain drug effects   physiology   growth & development   MeSH
• Animals MeSH
• Check Tag
• History, 20th Century MeSH
• History, 21st Century MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Historical Article MeSH
• Review MeSH
• Geographicals
• Czech Republic MeSH

The present study aimed to elucidate the effect of sulforaphane (a natural isothiocyanate) on oxidative stress and mitochondrial dysfunction during and at selected periods following status epilepticus (SE) induced in immature 12-day-old rats by Li-pilocarpine. Dihydroethidium was employed for the detection of superoxide anions, immunoblot analyses for 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) levels and respiratory chain complex I activity for evaluation of mitochondrial function. Sulforaphane was given i.p. in two doses (5 mg/kg each), at PD 10 and PD 11, respectively. The findings of the present study indicate that both the acute phase of SE and the early period of epileptogenesis (1 week and 3 weeks following SE induction) are associated with oxidative stress (documented by the enhanced superoxide anion production and the increased levels of 3-NT and 4-HNE) and the persisting deficiency of complex I activity. Pretreatment with sulforaphane either completely prevented or significantly reduced markers of both oxidative stress and mitochondrial dysfunction. Since sulforaphane had no direct anti-seizure effect, the findings suggest that the ability of sulforaphane to activate Nrf2 is most likely responsible for the observed protective effect. Nrf2-ARE signaling pathway can be considered a promising target for novel therapies of epilepsy, particularly when new compounds, possessing inhibitory activity against protein-protein interaction between Nrf2 and its repressor protein Keap1, with less "off-target" effects and, importantly, with an optimal permeability and bioavailability properties, become available commercially.

• Keywords
• Immature rats, Mitochondrial dysfunction, Oxidative stress, Protection, Status epilepticus, Sulforaphane,
• MeSH
• NF-E2-Related Factor 2 * metabolism   MeSH
• Isothiocyanates pharmacology   MeSH
• Kelch-Like ECH-Associated Protein 1 metabolism   MeSH
• Rats MeSH
• Mitochondria metabolism   MeSH
• Oxidative Stress MeSH
• Status Epilepticus * metabolism   MeSH
• Sulfoxides metabolism   pharmacology   MeSH
• Superoxides metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• NF-E2-Related Factor 2 * MeSH
• Isothiocyanates MeSH
• Kelch-Like ECH-Associated Protein 1 MeSH
• sulforaphane MeSH Browser
• Sulfoxides MeSH
• Superoxides MeSH

Perinatal hypoxic-ischemic insult (HII) is one of the main devastating causes of morbidity and mortality in newborns. HII induces brain injury which evolves to neurological sequelae later in life. Hypothermia is the only therapeutic approach available capable of diminishing brain impairment after HII. Finding a novel therapeutic method to reduce the severity of brain injury and its consequences is critical in neonatology. The present paper aimed to evaluate the effect of sulforaphane (SFN) pre-treatment on glucose metabolism, neurodegeneration, and functional outcome at the acute, sub-acute, and sub-chronic time intervals in the experimental model of perinatal hypoxic-ischemic insult in rats. To estimate the effect of SFN on brain glucose uptake we have performed 18F-deoxyglucose (FDG) microCT/PET. The activity of FDG was determined in the hippocampus and sensorimotor cortex. Neurodegeneration was assessed by histological analysis of Nissl-stained brain sections. To investigate functional outcomes a battery of behavioral tests was employed. We have shown that although SFN possesses a protective effect on glucose uptake in the ischemic hippocampus 24 h and 1 week after HII, no effect has been observed in the motor cortex. We have further shown that the ischemic hippocampal formation tends to be thinner in HIE and SFN treatment tends to reverse this pattern. We have observed subtle chronic movement deficit after HII detected by ladder rung walking test with no protective effect of SFN. SFN should be thus considered as a potent neuroprotective drug with the capability to interfere with pathophysiological processes triggered by perinatal hypoxic-ischemic insult.

• MeSH
• Fluorodeoxyglucose F18 therapeutic use   MeSH
• Glucose MeSH
• Hypoxia complications   MeSH
• Isothiocyanates MeSH
• Rats MeSH
• Brain diagnostic imaging   pathology   MeSH
• Hypoxia-Ischemia, Brain * diagnostic imaging   drug therapy   MeSH
• Animals, Newborn MeSH
• Brain Injuries * MeSH
• Sulfoxides MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Fluorodeoxyglucose F18 MeSH
• Glucose MeSH
• Isothiocyanates MeSH
• sulforaphane MeSH Browser
• Sulfoxides MeSH